The prognostic significance of the NMD core factor UPF1 in low-grade glioma

Abstract

Abstract Low-grade glioma (LGG) frequently occurring in children and adolescents. Upstream frameshift protein 1 (UPF1) is involved in nonsense-mediated mRNA decay (NMD), in LGG progression and tumor invasion remains unclear. Data from The Cancer Genome Atlas (TCGA) and GTEx were analyzed to compare UPF1 expression in normal and cancer tissues. Protein levels were studied using the Human Protein Atlas (HPA). Gene enrichment analyses were performed, alongside genetic, methylation, immune infiltration, and clinicopathological evaluations. Kaplan-Meier (KM) and receiver operating characteristic (ROC) curve analyses assessed UPF1’s prognostic value, and a nomogram for survival prediction was developed. UPF1 mRNA and protein levels were significantly higher in LGG tissues (P < 0.05). UPF1 expression was linked to tumor microenvironment and immune cell-related pathways. Genetic alterations in UPF1 impacted overall survival (OS), rather than disease-free survival. DNA methylation patterns of UPF1 had significant prognostic value. UPF1 expression level was correlated with immune cell infiltration (e.g., B cells, CD4 + T cells, macrophages). High UPF1 expression, advanced grade, gene mutations, older age, and unfavorable treatment outcomes were associated with poor OS (P < 0.05). The nomogram based on six risk factors exhibited moderate accuracy (AUC1-year = 0.680). UPF1 is a potential biomarker for tumor immune infiltration and prognosis in LGG patients.

Keywords

• UPF1
• Low-grade glioma
• Biomarkers
• Immune infiltration